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Preliminary data on phi production in central Pb + Pb collisions at 158 GeV per nucleon are presented, measured by the NA49 experiment in the hadronic decay channel phi - K+K-. At mid-rapidity, the kaons were separated from pions and protons by combining dE/dx and time-of-flight information; in the forward rapidity range only dE/dx identification was used to obtain the rapidity distribution and a rapidity-integrated mt-spectrum. The mid-rapidity yield obtained was dN/dy = 1.85 ± 0.3 per event; the total phi multiplicity was estimated to be 5.0 ± 0.7 per event. Comparison with published pp data shows a slight, but not very significant strangeness enhancement.
The large acceptance TPCs of the NA49 spectrometer allow for a systematic multidimensional study of two-particle correlations in different part of phase space. Results from Bertsch-Pratt and Yano-Koonin-Podgoretskii parametrizations are presented differentially in transverse pair momentum and pair rapidity. These studies give an insight into the dynamical space-time evolution of relativistic Pb+Pb collisions, which is dominated by longitudinal expansion.
Lambda and Antilambda reconstruction in central Pb+Pb collisions using a time projection chamber
(1997)
The large acceptance time projection chambers of the NA49 experiment are used to record the trajectory of charged particles from Pb + Pb collisions at 158 GeV per nucleon. Neutral strange hadrons have been reconstructed from their charged decay products. To obtain distributions of Λ, and Ks0 in discrete bins of rapidity, y, and transverse momentum, pT, calculations have been performed to determine the acceptance of the detector and the efficiency of the reconstruction software as a function of both variables. The lifetime distributions obtained give values of cτ = 7.8 ± 0.6 cm for Λ and cτ = 2.5 ± 0.3 cm for Ks0, consistent with data book values.
The transverse momentum and rapidity distributions of negative hadrons and participant protons have been measured for central 32S+ 32S collisions at plab=200 GeV/c per nucleon. The proton mean rapidity shift < Delta y>~1.6 and mean transverse momentum <pT>~0.6 GeV/c are much higher than in pp or peripheral AA collisions and indicate an increase in the nuclear stopping power. All pT spectra exhibit similar source temperatures. Including previous results for K0s Lambda , and Lambda -bar, we account for all important contributions to particle production.
The NA35 experiment has collected a high statistics set of momentum analyzed negative hadrons near and forward of midrapidity for central collisions of 200A GeV/c 32S+S, Cu, Ag, and Au. Using momentum space correlations to study the size of the source of particle production, the transverse source radii are found to decrease by ~40% at midrapidity and ~20% at forward rapidity while the longitudinal radius RL is found to decrease by ~50% as pT increases over the interval 50<pT<600 MeV/c. Calculations using a microscopic phase space approach (relativistic quantum molecular dynamics) reproduce the observed trends of the data. PACS: 25.75.+r
Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen–Conradi syndrome—a severe developmental disorder. Structures of Nep1 revealed a dimer with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this putative methyltransferase activity has not been identified yet. We characterized the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence- and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with high affinity to short RNA oligonucleotides corresponding to nt 910–921 of M. jannaschii 16S rRNA through a highly conserved basic surface cleft along the dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a position corresponding to a previously identified hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) in eukaryotic 18S rRNAs. Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR shows that the methyl group is transferred to the N1 of the pseudouridine. Thus, Nep1 is the first identified example of an N1-specific pseudouridine methyltransferase. This enzymatic activity is also conserved in human Nep1 suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Psi in eukaryotic 18S rRNAs.
The yeast fatty acid synthase (FAS) is a barrel-shaped 2.6 MDa complex. Upon barrel-formation, two multidomain subunits, each more than 200 kDa large, intertwine to form a heterododecameric complex that buries 170,000 Å2 of protein surface. In spite of the rich knowledge about yeast FAS in structure and function, its assembly remained elusive until recently, when co-translational interaction of the β-subunit with the nascent α-subunit was found to initiate assembly. Here, we characterize the co-translational assembly of yeast FAS at a molecular level. We show that the co-translationally formed interface is sensitive to subtle perturbations, so that the exchange of two amino acids located in the emerging interface can prevent assembly. On the other hand, assembly can also be initiated via the co-translational interaction of the subunits at other sites, which implies that this process is not strictly site or sequence specific. We further highlight additional steps in the biogenesis of yeast FAS, as the formation of a dimeric subunit that orchestrates complex formation and acts as platform for post-translational phosphopantetheinylation. The presented data supports the understanding of the recently discovered prevalence of eukaryotic complexes for co-translational assembly, and is valuable for further harnessing FAS in the biotechnological production of aliphatic compounds.
Archaea are motile by the rotation of the archaellum. The archaellum switches between clockwise and counterclockwise rotation, and movement along a chemical gradient is possible by modulation of the switching frequency. This modulation involves the response regulator CheY and the archaellum adaptor protein CheF. In this study, two new crystal forms and protein structures of CheY are reported. In both crystal forms, CheY is arranged in a domain-swapped conformation. CheF, the protein bridging the chemotaxis signal transduction system and the motility apparatus, was recombinantly expressed, purified and subjected to X-ray data collection.
The Nep1 (Emg1) SPOUT-class methyltransferase is an essential ribosome assembly factor and the human Bowen–Conradi syndrome (BCS) is caused by a specific Nep1D86G mutation. We recently showed in vitro that Methanocaldococcus jannaschii Nep1 is a sequence-specific pseudouridine-N1-methyltransferase. Here, we show that in yeast the in vivo target site for Nep1-catalyzed methylation is located within loop 35 of the 18S rRNA that contains the unique hypermodification of U1191 to 1-methyl-3-(3-amino-3-carboxypropyl)-pseudouri-dine (m1acp3Psi). Specific 14C-methionine labelling of 18S rRNA in yeast mutants showed that Nep1 is not required for acp-modification but suggested a function in Psi1191 methylation. ESI MS analysis of acp-modified Psi-nucleosides in a DeltaNep1-mutant showed that Nep1 catalyzes the Psi1191 methylation in vivo. Remarkably, the restored growth of a nep1-1ts mutant upon addition of S-adenosylmethionine was even observed after preventing U1191 methylation in a deltasnr35 mutant. This strongly suggests a dual Nep1 function, as Psi1191-methyltransferase and ribosome assembly factor. Interestingly, the Nep1 methyltransferase activity is not affected upon introduction of the BCS mutation. Instead, the mutated protein shows enhanced dimerization propensity and increased affinity for its RNA-target in vitro. Furthermore, the BCS mutation prevents nucleolar accumulation of Nep1, which could be the reason for reduced growth in yeast and the Bowen-Conradi syndrome.
Flavins are employed to transform physical input into biological output signals. In this function, flavins catalyze a variety of light-induced reactions and redox processes. However, nature also provides flavoproteins with the ability to uncouple the mediation of signals. Such proteins are the riboflavin-binding proteins (RfBPs) with their function to store riboflavin for fast delivery of FMN and FAD. Here we present in vitro and in vivo data showing that the recently discovered archaeal dodecin is an RfBP, and we reveal that riboflavin storage is not restricted to eukaryotes. However, the function of the prokaryotic RfBP dodecin seems to be adapted to the requirement of a monocellular organism. While in eukaryotes RfBPs are involved in trafficking riboflavin, and dodecin is responsible for the flavin homeostasis of the cell. Although only 68 amino acids in length, dodecin is of high functional versatility in neutralizing riboflavin to protect the cellular environment from uncontrolled flavin reactivity. Besides the predominant ultrafast quenching of excited states, dodecin prevents light-induced riboflavin reactivity by the selective degradation of riboflavin to lumichrome. Coordinated with the high affinity for lumichrome, the directed degradation reaction is neutral to the cellular environment and provides an alternative pathway for suppressing uncontrolled riboflavin reactivity. Intriguingly, the different structural and functional properties of a homologous bacterial dodecin suggest that dodecin has different roles in different kingdoms of life.
Dodecins, a group of flavin-binding proteins with a dodecameric quaternary structure, are able to incorporate two flavins within each of their six identical binding pockets building an aromatic tetrade with two tryptophan residues. Dodecin from the archaeal Halobacterium salinarum is a riboflavin storage device. We demonstrate that unwanted side reactions induced by reactive riboflavin species and degradation of riboflavin are avoided by ultrafast depopulation of the reactive excited state of riboflavin. Intriguingly, in this process, the staggered riboflavin dimers do not interact in ground and photoexcited states. Rather, within the tetrade assembly, each riboflavin is kept under the control of the respective adjacent tryptophan, which suggests that the stacked arrangement is a matter of optimizing the flavin load. We further identify an electron transfer in combination with a proton transfer as a central element of the effective excited state depopulation mechanism. Structural and functional comparisons of the archaeal dodecin with bacterial homologs reveal diverging evolution. Bacterial dodecins bind the flavin FMN instead of riboflavin and exhibit a clearly different binding pocket design with inverse incorporations of flavin dimers. The different adoption of flavin changes photochemical properties, making bacterial dodecin a comparably less efficient quencher of flavins. This supports a functional role different for bacterial and archaeal dodecins.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
Background: According to current taxonomy only three out of 27 Sinohimalayan leaf warbler species (Phylloscopidae) are considered genetically uniform across their entire breeding range along the Southeastern margin of the Qinghai-Tibetan Plateau, the Buff-barred Warbler (Phylloscopus pulcher) being one of them. Because marked differentiation among Himalayan and Chinese populations has been recently demonstrated for a number of Phylloscopus species (or sister species) we investigated the intraspecific variation of a mitochondrial gene, songs and morphology of P. pulcher in a phylogeographic approach.
Methods: We sequenced a fragment of the mitochondrial cytochrome b, reconstructed haplotype networks and analyzed DNA polymorphism among Himalayan and Chinese populations. We measured time and frequency parameters of two distinct song types and analyzed among population-differentiation in a principal component analysis and a discriminant analysis. We also compared measurements of body size dimensions taken from museum specimens.
Results: The mitochondrial haplotype network (cytb) was divided into two distinct clusters corresponding to geographic origin of samples. Pairwise genetic distances among Himalayan and Chinese mtDNA lineages account for 1.3% which coincides with Pleistocene lineage separation at roughly 650,000 years ago. Genetic diversity is slightly higher in the Chinese part of the species’ range with respect to haplotype and nucleotide diversity while the less diversified Himalayan population lineage shows signs of recent range expansion. The vocal repertoire of P. pulcher comprises two distinct verse types that are combined with short interspersed click notes to long continuous song displays. Trill verse types showed significant differences among regions in almost all measured frequency and time parameters: Chinese males displayed more rapid and more broad-banded trills at a lower pitch. In contrast, warbling verse types showed a distinctively different structure among regions: Himalayan songs consisted of repeated syllables while Chinese songs comprised repetitions of single, long and strongly modulated elements. Subtle morphological differences among specimens from the two study regions could only be confirmed for plumage coloration but not for metric characters.
Conclusions: Based on the genetic and bioacoustic distinctiveness of Chinese Buff-barred Warbler populations, we recommend that the name Phylloscopus pulcher vegetus Bangs, 1913 should be re-validated for this taxon.
Songs in passerine birds are important for territory defense and mating. Speciation rates in oscine passerines are so high, due to cultural evolution, that this bird lineage makes up half of the extant bird species. Leaf warblers are a speciose Old-World passerine family of limited morphological differentiation, so that songs are even more important for species delimitation. We took 16 sonographic traits from song recordings of 80 leaf warbler taxa and correlated them with 15 potentially explanatory variables, pairwise, and in linear models. Based on a well-resolved molecular phylogeny of the same taxa, all pairwise correlations were corrected for relatedness with phylogenetically independent contrasts and phylogenetic generalized linear models were used. We found a phylogenetic signal for most song traits, but a strong one only for the duration of the longest and of the shortest element, which are presumably inherited instead of learned. Body size of a leaf warbler species is a constraint on song frequencies independent of phylogeny. At least in this study, habitat density had only marginal impact on song features, which even disappeared through phylogenetic correction. Maybe most leaf warblers avoid the deterioration through sound propagation in dense vegetation by singing from exposed perches. Latitudinal (and longitudinal) extension of the breeding ranges was correlated with most song features, especially verse duration (longer polewards and westwards) and complexity (lower polewards). Climate niche or expansion history might explain these correlations. The number of different element types per verse decreases with elevation, possibly due to fewer resources and congeneric species at higher elevations.
Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.
The authors review the current status of percutaneous left atrial appendage (LAA) occlusion therapy in patients with atrial fibrillation with the goal to prevent ischemic stroke and systemic embolism and to reduce oral anticoagulation associated bleeding. While we cover the historical and also surgical background, and all tested devices, the main focus rests on the single currently U.S. Food and Drug Administration (FDA) approved LAA occluder, the WATCHMAN device, and its approval process. The authors also give a critical appraisal beyond the review of mere facts, trying to put the current data into perspective.
The optimal treatment strategy for secondary prevention in patients with cryptogenic stroke and patent foramen ovale (PFO) has been a matter of controversy for decades. After three randomized trials failed to show a benefit of closure with an excess of complications in the interventional arm, two large recent trials suggest a benefit with regard of preventing further ischemic strokes. With this discrepancy in results it is important to discuss recent trials in detail and evolve an informed clinical approach for daily practice.
Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.